Real-world effectiveness of the heterologous SOBERANA-02 and SOBERANA-Plus vaccine scheme in 2-11 years-old children during the SARS-CoV-2 Omicron wave in Cuba: a longitudinal case-population study.

Background: Increased pediatric COVID-19 occurrence due to the SARS-CoV-2 Omicron variant has raised concerns about the effectiveness of existing vaccines. The protection provided by the SOBERANA-02-Plus vaccination scheme against this variant has not yet been studied. We aimed to evaluate the scheme's effectiveness against symptomatic Omicron infection and severe disease in children. Methods: In September 2021, Cuba implemented a mass pediatric immunization with the heterologous SOBERANA-02-Plus scheme: 2 doses of conjugated SOBERANA-02 followed by a heterologous SOBERANA-Plus dose. By December, before the Omicron outbreak, 95.4% of 2-18 years-old had been fully immunized. During the entire Omicron wave, we conducted a nationwide longitudinal post-vaccination case-population study to evaluate the real-world effectiveness of the SOBERANA-02-Plus scheme against symptomatic infection and severe disease in children without previous SARS-CoV-2 infection. The identification of COVID-19 cases relied on surveillance through first line services, which refer clinical suspects to pediatric hospitals where they are diagnosed based on a positive RT-PCR test. We defined the Incidence Rate ratio (IRR) as IRvaccinated age group/IRunvaccinated 1-year-old and calculated vaccine effectiveness as VE = (1-IRR)∗100%. 24 months of age being the 'eligible for vaccination' cut-off, we used a regression discontinuity approach to estimate effectiveness by contrasting incidence in all unvaccinated 1-year-old versus vaccinated 2-years-old. Estimates in the vaccinated 3-11 years-old are reported from a descriptive perspective. Findings: We included 1,098,817 fully vaccinated 2-11 years-old and 98,342 not vaccinated 1-year-old children. During the 24-week Omicron wave, there were 7003/26,241,176 person-weeks symptomatic COVID-19 infections in the vaccinated group (38.2 per 105 person-weeks in 2-years-old and 25.5 per 105 person-weeks in 3-11 years-old) against 3577/2,312,273 (154.7 per 105 person-weeks) in the unvaccinated group. The observed overall vaccine effectiveness against symptomatic infection was 75.3% (95% CI, 73.5-77.0%) in 2-years-old children, and 83.5% (95% CI, 82.8-84.2%) in 3-11 years-old. It was somewhat lower during Omicron BA.1 then during Omicron BA.2 variant circulation, which took place 1-3 and 4-6 months after the end of the vaccination campaign. The effectiveness against severe symptomatic disease was 100.0% (95% CI not estimated) and 94.6% (95% CI, 82.0-98.6%) in the respective age groups. No child death from COVID-19 was observed. Interpretation: Immunization of 2-11 years-old with the SOBERANA-02-Plus scheme provided strong protection against symptomatic and severe disease caused by the Omicron variant, which was sustained during the six months post-vaccination follow-up. Our results contrast with the observations in previous real-world vaccine effectiveness studies in children, which might be explained by the type of immunity a conjugated protein-based vaccine induces and the vaccination strategy used. Funding: National Fund for Science and Technology (FONCI-CITMA-Cuba).

Risk factors for pulmonary tuberculosis recurrence, relapse and reinfection: a systematic review and meta-analysis.

BACKGROUND: The rate of pulmonary tuberculosis (TB) recurrence is substantial. Identifying risk factors can support the development of prevention strategies. METHODS: We retrieved studies published between 1 January 1980 and 31 December 2022 that assessed factors associated with undifferentiated TB recurrence, relapse or reinfection. For factors reported in at least four studies, we performed random-effects meta-analysis to estimate a pooled relative risk (RR). We assessed heterogeneity, risk of publication bias and certainty of evidence. RESULTS: We included 85 studies in the review; 81 documented risk factors for undifferentiated recurrence, 17 for relapse and 10 for reinfection. The scope for meta-analyses was limited given the wide variety of factors studied, inconsistency in control for confounding and the fact that only few studies employed molecular genotyping. Factors that significantly contributed to moderately or strongly increased pooled risk and scored at least moderate certainty of evidence were: for undifferentiated recurrence, multidrug resistance (MDR) (RR 3.49; 95% CI 1.86 to 6.53) and fixed-dose combination TB drugs (RR 2.29; 95% CI 1.10 to 4.75) in the previous episode; for relapse, none; and for reinfection, HIV infection (RR 4.65; 95% CI 1.71 to 12.65). Low adherence to treatment increased the pooled risk of recurrence 3.3-fold (95% CI 2.37 to 4.62), but the certainty of evidence was weak. CONCLUSION: This review emphasises the need for standardising methods for TB recurrence research. Actively pursuing MDR prevention, facilitating retention in treatment and providing integrated care for patients with HIV could curb recurrence rates. The use of fixed-dose combinations of TB drugs under field conditions merits further attention. PROSPERO REGISTRATION NUMBER: CRD42018077867.

The Potential of Surveillance Data for Dengue Risk Mapping: An Evaluation of Different Approaches in Cuba.

To better guide dengue prevention and control efforts, the use of routinely collected data to develop risk maps is proposed. For this purpose, dengue experts identified indicators representative of entomological, epidemiological and demographic risks, hereafter called components, by using surveillance data aggregated at the level of Consejos Populares (CPs) in two municipalities of Cuba (Santiago de Cuba and Cienfuegos) in the period of 2010-2015. Two vulnerability models (one with equally weighted components and one with data-derived weights using Principal Component Analysis), and three incidence-based risk models were built to construct risk maps. The correlation between the two vulnerability models was high (tau > 0.89). The single-component and multicomponent incidence-based models were also highly correlated (tau ≥ 0.9). However, the agreement between the vulnerability- and the incidence-based risk maps was below 0.6 in the setting with a prolonged history of dengue transmission. This may suggest that an incidence-based approach does not fully reflect the complexity of vulnerability for future transmission. The small difference between single- and multicomponent incidence maps indicates that in a setting with a narrow availability of data, simpler models can be used. Nevertheless, the generalized linear mixed multicomponent model provides information of covariate-adjusted and spatially smoothed relative risks of disease transmission, which can be important for the prospective evaluation of an intervention strategy. In conclusion, caution is needed when interpreting risk maps, as the results vary depending on the importance given to the components involved in disease transmission. The multicomponent vulnerability mapping needs to be prospectively validated based on an intervention trial targeting high-risk areas.

Safety and efficacy of the two doses conjugated protein-based SOBERANA-02 COVID-19 vaccine and of a heterologous three-dose combination with SOBERANA-Plus: a double-blind, randomised, placebo-controlled phase 3 clinical trial.

Background: SOBERANA-02 is a COVID-19 conjugate vaccine (recombinant RBD conjugated to tetanus toxoid). Phases 1/2 clinical trials demonstrated high immunogenicity, promoting neutralising IgG and specific T-cell response. A third heterologous dose of SOBERANA-Plus (RBD-dimer) further increased neutralising antibodies. The aim of this study is to evaluate the safety and efficacy of two immunisation regimes: two doses of SOBERANA-02 and a heterologous three-dose combination with SOBERANA-Plus added to it. Methods: From March 8th to June 24th, 2021 we conducted in Havana, Cuba a multicentre randomised, double-blind, placebo-controlled, phase-3 trial evaluating a two doses SOBERANA-02 scheme and a heterologous scheme with one dose SOBERANA-Plus added to it (RPCEC00000354). Participants 19-80 years were randomly assigned to receiving 28 days apart either the two or three dose scheme or placebo. The main endpoint was vaccine efficacy in preventing the occurrence of RT-PCR confirmed symptomatic COVID-19 at least 14 days after the second or third dose in the per-protocol population. We also assessed efficacy against severe disease and, in all participants receiving at least one vaccine/placebo dose, safety for 28 days after each dose. Findings: We included 44,031 participants (52.0% female, 48.0% male; median age 50 years, range 19-80 years; 7.0% black, 24.0% mixed-race, 59.0% white) in a context of initial Beta VOC predominance, with this variant being partially replaced by Delta near the trial's end. Vaccine efficacy in the heterologous combination was 92.0% (95%CI 80.4-96.7) against symptomatic disease. There were no severe COVID-19 cases in the vaccine group against 6 in the placebo group. Two doses of SOBERANA-02 was 69.7% (95%CI 56.5-78.9) and 74.9% (95%CI 33.7-90.5) efficacious against symptomatic and severe COVID-19, respectively. The occurrence of serious and severe adverse events (AE) was very rare and equally distributed between placebo and vaccine groups. Solicited AEs were slightly more frequent in the vaccine group but predominantly local and mostly mild and transient. Interpretation: Our results indicate that the straightforward to manufacture SOBERANA vaccines are efficacious in a context of Beta and Delta VOC circulation, have a favourable safety profile, and may represent an attractive option for use in COVID-19 vaccination programmes. Funding: This study received funds from the National Fund for Science and Technology (FONCI-CITMA-Cuba, contract 2020-20) of the Ministry of Science, Technology and Environment of Cuba.

Effectiveness of a provider and patient-focused intervention to improve hypertension management and control in the primary health care setting in Cuba: a controlled before-after study.

BACKGROUND: Implementation research to improve hypertension control is scarce in Latin America. We assessed the effectiveness of an intervention aimed at primary care practitioners and hypertensive patients in a setting that provides integrated care through an accessible network of family practices. METHODS: We conducted in Cardenas and Santiago, Cuba, a controlled before-after study in 122 family practices, which are staffed with a doctor and a nurse. The intervention comprised a control arm (usual care), an arm with a component targeting providers (hypertension management workshops), and an arm with, on top of the latter, a component targeting patients (hypertension schools). To evaluate the effect, we undertook a baseline survey before the intervention and an endline survey sixteen months after its start. In each survey, we randomly included 1400 hypertensive patients. Controlled hypertension, defined as a mean systolic and diastolic blood pressure below 140 and 90 mmHg, respectively, was the primary endpoint assessed. We performed linear and logistic regression with a Generalized Estimating Equations approach to determine if the proportion of patients with controlled hypertension changed following the intervention. RESULTS: Seventy-three doctors, including substitutes, and 54 nurses from the 61 intervention family practices attended the provider workshops, and 3308 patients -51.6% of the eligible ones- participated in the hypertension schools. Adherence to anti-hypertensive medication improved from 42% at baseline to 63% at the endline in the intervention arms. Under the provider intervention, the proportion of patients with controlled hypertension increased by 18.9%, from 48.7% at baseline to 67.6% at endline. However, adding the component that targeted hypertensive patients did not augment the effect. Compared to patients in the control arm, the adjusted OR of having controlled hypertension was 2.36 (95% CI, 1.73-3.22) in the provider and 2.00 (95% CI, 1.68-2.37) in the provider plus patient intervention arm. CONCLUSIONS: The intervention's patient component remains to be fine-tuned. Still, we demonstrate that it is feasible to substantially improve hypertension outcomes by intervention at the primary care level, despite an already relatively high control rate.

Protocol for a controlled before-after quasi-experimental study to evaluate the effectiveness of a multi-component intervention to reduce gaps in hypertension care and control in low-income communes of Medellin, Colombia.

INTRODUCTION: Research on public health interventions to improve hypertension care and control in low-income and middle-income countries remains scarce. This study aims to evaluate the effectiveness and assess the process and fidelity of implementation of a multi-component intervention to reduce the gaps in hypertension care and control at a population level in low-income communes of Medellin, Colombia. METHODS AND ANALYSIS: A multi-component intervention was designed based on international guidelines, cross-sectional population survey results and consultation with the community and institutional stakeholders. Three main intervention components integrate activities related to (1) health services redesign, (2) clinical staff training and (3) patient and community engagement. The effectiveness of the intervention will be evaluated in a controlled before-after quasi-experimental study, with two deprived communes of the city selected as intervention and control arms. We will conduct a baseline and an endline survey 2 years after the start of the intervention. The primary outcomes will be the gaps in hypertension diagnosis, treatment, follow-up and control. Effectiveness will be evaluated with the difference-in-difference measures. Generalised estimation equation models will be fitted considering the clustered nature of data and adjusting for potential confounding variables. The implementation process will be studied with mixed methods. Implementation fidelity will be documented to assess to which degree the intervention components were implemented as intended. ETHICS AND DISSEMINATION: The study protocol has been approved by the Ethics Research Committee of Metrosalud in Colombia (reference 1400/5.2), the Medical Ethics Committee of the Antwerp University Hospital (reference 18/40/424) and the Institutional Review Board of the Antwerp Institute of Tropical Medicine (reference 1294/19). We will share and discuss the study results with the community, institutional stakeholders and national health policymakers. We will publish them in national and international peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT05011838.

Lung cancer occurrence after an episode of tuberculosis: a systematic review and meta-analysis.

INTRODUCTION: People with tuberculosis experience long-term health effects beyond cure, including chronic respiratory diseases. We investigated whether tuberculosis is a risk factor for subsequent lung cancer. METHODS: We searched PubMed, Scopus, Cochrane, Latin American and Caribbean Health Sciences Literature and the Scientific Electronic Library Online for cohort and case-control studies providing effect estimates for the association between tuberculosis and subsequent lung cancer. We pooled estimates through random-effects meta-analysis. The study was registered in PROSPERO (CDR42020178362). RESULTS: Out of 6240 records, we included 29 cohort and 44 case-control studies. Pooled estimates adjusted for age and smoking (assessed quantitatively) were hazard ratio (HR) 1.51 (95% CI 1.30-1.76, I2=81%; five studies) and OR 1.74 (95% CI 1.42-2.13, I2=59%; 19 studies). The occurrence of lung cancer was increased for 2 years after tuberculosis diagnosis (HR 5.01, 95% CI 3.64-6.89; two studies), but decreased thereafter. Most studies were retrospective, had moderate to high risk of bias, and did not control for passive smoking, environmental exposure and socioeconomic status. Heterogeneity was high. CONCLUSION: We document an association between tuberculosis and lung cancer occurrence, particularly in, but not limited to, the first 2 years after tuberculosis diagnosis. Some cancer cases may have been present at the time of tuberculosis diagnosis and therefore causality cannot be ascertained. Prospective studies controlling for key confounding factors are needed to identify which tuberculosis patients are at the highest risk, as well as cost-effective approaches to mitigate such risk.

Intervención multicomponente para la reducción de las brechas en el proceso de atención y control de la hipertensión / Multicomponent Intervention to Reduce Gaps in the Hypertension Care and Control Process

RESUMEN Fundamento las evidencias sobre intervenciones de Salud Pública para mejorar las deficiencias en la atención y control de las personas hipertensas continúan siendo insuficientes. Objetivo implementar una intervención multicomponente para reducir dichas brechas en el Policlínico Julio Antonio Mella del municipio de Guanabacoa, evaluar el proceso de intervención, su efectividad y la fidelidad de su implementación. Método en relación a los resultados obtenidos en el estudio de base y recomendaciones técnicas nacionales e internacionales, se diseñó una intervención multicomponente que contará con los siguientes componentes: reorganización de los servicios de salud, capacitación del personal de salud, empoderamiento de los pacientes y participación de la comunidad. La efectividad de la intervención se evaluará por medio de un estudio cuasi-experimental (antes y después). La intervención cubrirá el policlínico antes mencionado, los diez consultorios del estudio de base y la población atendida por ellos. A los dos años de iniciada la implementación se aplicará nuevamente una encuesta poblacional y se estimará la diferencia en la magnitud de las brechas poblacionales pre-post intervención, además se monitoreará el proceso y se evaluará la fidelidad de la implementación de la intervención. Resultados reducir las brechas existentes en el proceso de atención al paciente hipertenso, identificar su magnitud en relación a la línea base. Conclusiones el estudio brindará evidencias al Ministerio de Salud Pública cubano y a otros países, especialmente de América Latina, para mejorar el cuidado del paciente con padecimientos crónicos.

ABSTRACT Background: the evidence on Public Health interventions to improve deficiencies in the care and control of hypertensive people continues to be insufficient. Objective: to implement a multicomponent intervention to reduce these gaps in the Julio Antonio Mella Polyclinic in the Guanabacoa municipality, to evaluate the intervention process, its effectiveness and the fidelity of its implementation. Method: in relation to the results obtained in the baseline study, national and international technical recommendations, a multicomponent intervention was designed that will have the following components: reorganization of health services, training of health personnel, empowerment of patients and community participation. The effectiveness of the intervention will be evaluated through a quasi-experimental study (before and after). The intervention will cover the aforementioned polyclinic, the ten baseline study clinics, and the population served by them. Two years after the start of implementation, a population survey will be applied again and the difference in the magnitude of the pre-post intervention population gaps will be estimated. In addition, the process will be monitored and the fidelity of the implementation of the intervention will be evaluated. Results: reduce existing gaps in the process of care for hypertensive patients, identify their magnitude in relation to the baseline. Conclusions: the study will provide evidence to the Cuban Ministry of Public Health and other countries, especially in Latin America, to improve the care of chronic patients.

Gaps in Hypertension Management in a Middle-Income Community of Quito-Ecuador: A Population-Based Study.

Optimal hypertension care and control at population level significantly reduces cardiovascular morbidity and mortality. The study objective was to measure the gaps in the diagnosis, care, and control of hypertension in residents of an urban community in Quito, Ecuador. A cross-sectional population-based study with a sample of 2160 persons was performed using a survey and direct blood pressure measurement. Logistical regression models were used for analyzing factors associated with the gaps, expressed as percentages. The prevalence of hypertension was 17.6% [CI 95% 17.3-17.9%]. The diagnosis gap was 6.1% [CI 95% 5.9-6.2%] among the entire population and 34.5% [CI 95% 33.7-35.3%] among persons with hypertension. No access gaps were detected; whereas the follow-up gap was 22.7% [CI 95% 21.8-23.6%] and control gap reached 43.5% [CI 95% 42.6-44.2%]. Results indicated that being male, older than 64 years, an employee, without health insurance, and not perceiving a need for healthcare, increased the risk of experiencing these gaps. Data showed appropriate access to health services and high coverage in the diagnosis was due to the application of a community and family healthcare model. Notwithstanding, we found significant gaps in the follow-up and control of hypertensive patients, especially among older males, which should warrant the attention of the Ministry of Health.

Evaluation of insecticide treated window curtains and water container covers for dengue vector control in a large-scale cluster-randomized trial in Venezuela.

BACKGROUND: Following earlier trials indicating that their potential in dengue vector control was constrained by housing structure, a large-scale cluster-randomized trial of insecticide treated curtains (ITCs) and water jar covers (ITJCs) was undertaken in Venezuela. METHODS: In Trujillo, Venezuela, 60 clusters (6223 houses total) were randomized so that 15 clusters each received either PermaNet insecticide-treated window curtains (ITCs), permanent insecticide-treated water storage jar covers (ITJCs), a combination of both ITCs and ITJCs, or no insecticide treated materials (ITMs). A further 15 clusters located at least 5km from the edge of the study site were selected to act as an external control. Entomological surveys were carried out immediately before and after intervention, and then at 6-month intervals over the following 27 months. The Breteau and House indices were used as primary outcome measures and ovitrap indices as secondary. Negative binomial regression models were used to compare cluster-level values of these indices between the trial arms. RESULTS: Reductions in entomological indices followed deployment of all ITMs and throughout the trial, indices in the external control arm remained substantially higher than in the ITM study arms including the internal control. Comparing the ratios of between-arm means to summarise the entomological indices throughout the study, the combined ITC+ITJC intervention had the greatest impact on the indices, with a 63% difference in the pupae per person indices between the ITC+ITJC arm and the internal control. However, coverage had fallen below 60% by 14-months post-intervention and remained below 40% for most of the remaining study period. CONCLUSIONS: ITMs can impact dengue vector populations in the long term, particularly when ITCs and ITJCs are deployed in combination. TRIAL REGISTRATION: ClinicalTrials.gov ISRCTN08474420; www.isrctn.com.

Gaps in hypertension care and control: a population-based study in low-income urban Medellin, Colombia.

OBJECTIVES: To assess hypertension prevalence and the extent and associated factors of hypertension diagnosis, follow-up, treatment and control gaps in low-income urban Medellin, Colombia. METHODS: We randomly sampled 1873 adults aged 35 or older. Unaware hypertensive individuals were defined as those without previous diagnosis whose average blood pressure was equal to or above 140/90 mmHg. For aware hypertensive patients, control was delimited as average blood pressure below 140/90 if under 59 years old or diabetic, and as less than 150/90 otherwise. We used logistic regression to identify care gap-associated factors. RESULTS: Hypertension prevalence was 43.5% (95% CI 41.2-45.7). We found 28.2% aware and 15.3% unaware hypertensive individuals, which corresponds to a 35.1% (95% CI 31.9-38.5) underdiagnosis. This gap was determined by age, sex, education and lifestyle factors. 14.4% (95% CI 11.6-17.6) of aware hypertensive patients presented a follow-up gap, 93.4% (95% CI 90.9-95.2) were prescribed antihypertensive drugs, but 38.9% (95% CI 34.7-43.3) were not compliant. The latter was strongly associated with follow-up. The hypertension control gap in aware hypertensive patients, 39.0% (95% CI: 34.9-43.2), was associated with being older, having diabetes, weakly adhering to pharmacological treatment and receiving poor non-pharmacological advice. Overall, 60.4% (95% CI 57.0-63.8) of aware and unaware hypertensive participants had either diagnosed but uncontrolled or undiagnosed hypertension. CONCLUSIONS: We found high hypertension prevalence coupled with, from an international perspective, encouraging awareness and control figures. Still, there remains ample room for improvement. Our findings can assist in designing integrated primary healthcare measures that further strengthen equitable and effective access to hypertension care and control.

Recurrent TB: a systematic review and meta-analysis of the incidence rates and the proportions of relapses and reinfections.

BACKGROUND: A recurrent tuberculosis (TB) episode results from exogenous reinfection or relapse after cure. The use of genotyping allows the distinction between both. METHODS: We did a systematic review and meta-analysis, using four databases to search for studies in English, French and Spanish published between 1 January 1980 and 30 September 2020 that assessed recurrences after TB treatment success and/or differentiated relapses from reinfections using genotyping. We calculated person years of follow-up and performed random-effects model meta-analysis for estimating pooled recurrent TB incidence rates and proportions of relapses and reinfections. We performed subgroup analyses by clinical-epidemiological factors and by methodological study characteristics. FINDINGS: The pooled recurrent TB incidence rate was 2.26 per 100 person years at risk (95% CI 1.87 to 2.73; 145 studies). Heterogeneity was high (I2=98%). Stratified pooled recurrence rates increased from 1.47 (95% CI 0.87 to 2.46) to 4.10 (95% CI 2.67 to 6.28) per 100 person years for studies conducted in low versus high TB incidence settings. Background HIV prevalence, treatment drug regimen, sample size and duration of follow-up contributed too. The pooled proportion of relapses was 70% (95% CI 63% to 77%; I²=85%; 48 studies). Heterogeneity was determined by background TB incidence, as demonstrated by pooled proportions of 83% (95% CI 75% to 89%) versus 59% (95% CI 42% to 74%) relapse for studies from settings with low versus high TB incidence, respectively. INTERPRETATION: The risk of recurrent TB is substantial and relapse is consistently the most frequent form of recurrence. Notwithstanding, with increasing background TB incidence the proportion of reinfections increases and the predominance of relapses among recurrences decreases. PROSPERO REGISTRATION NUMBER: CRD42018077867.

Out-of-pocket expenditure for hypertension care: a population-based study in low-income urban Medellin, Colombia.

Background Hypertension requires life-long medical care, which may cause economic burden and even lead to catastrophic health expenditure. Objective To estimate the extent of out-of-pocket expenditure for hypertension care at a population level and its impact on households' budgets in a low-income urban setting in Colombia. Methods We conducted a cross-sectional survey in Santa Cruz, a commune in the city of Medellin. In 410 randomly selected households with a hypertensive adult, we estimated annual basic household expenditure and hypertension-attributable out-of-pocket expenditure. For socioeconomic stratification, we categorised households according to basic expenditure quintiles. Catastrophic hypertension-attributable expenditure was defined as out-of-pocket expenditure above 10% of total household expenditure. Results The average annual basic household expenditure was US dollars at purchasing power parity (USD-PPP) $12,255.59. The average annual hypertension-attributable out-of-pocket expenditure was USD-PPP $147.75 (95% CI 120.93-174.52). It was incurred by 73.9% (95% CI 69.4%-78.1%) of patients, and consisted mainly of direct non-medical expenses (76.7%), predominantly for dietary requirements prescribed as non-pharmacological treatment and for transport to attend health care consultations. Medical out-of-pocket expenditure (23.3%) was for the most part incurred for pharmacological treatment. Hypertension-attributable out-of-pocket expenditure represented on average 1.6% (95% CI 1.3%-1.9%) of the total annual basic household expenditure. Eight households (2.0%; 95% CI 1.0%-3.8%) had catastrophic health expenditure; six of them belonged to the two lowest expenditure quintiles. Payments related to dietary requirements and transport to consultations were critical determinants of their catastrophic expenditure. Conclusions Out-of-pocket expenditure for hypertension care is moderate on average, but frequent, and mainly made up of direct non-medical expenses. Catastrophic health expenditure is uncommon and affects primarily households in the bottom socioeconomic quintiles. Financial protection should be strengthened by covering the costs of chronic diseases-related dietary requirements and transport to health services in the most deprived households. Abbreviations NCDs: Non-communicable diseases; LMICs: Low and middle-income countries; WHO: World Health Organization; HTN: hypertension; CVDs: Cardiovascular diseases; OOPE: out-of-pocket expenditure; USD-PPP: US dollars at purchasing power parity; CI: Confidence interval.

Contact evaluation and isoniazid preventive therapy among close and household contacts of tuberculosis patients in Lima, Peru: an analysis of routine data.

OBJECTIVE: Contacts of pulmonary tuberculosis (TB) cases are at high risk of TB infection and progression to disease. Close and household contacts and those <5 years old have the highest risk. Isoniazid preventive therapy (IPT) can largely prevent TB disease among infected individuals. International and Peruvian recommendations include TB contact investigation and IPT prescription to eligible contacts. We conducted a study in Lima, Peru, to determine the number of close and household contacts who were evaluated, started on IPT, and who completed it, and the factors associated to compliance with national guidelines. METHODS: We conducted a longitudinal retrospective study including all TB cases diagnosed between January 2015 and July 2016 in 13 health facilities in south Lima. Treatment cards, TB registers and clinical files were reviewed and data on index cases (sex, age, smear status, TB treatment outcome), contact investigation (sex, age, kinship to the index case, evaluations at month 0, 2 and 6) and health facility (number of TB cases notified per year, proportion of TB cases with treatment success) were extracted. We tabulated frequencies of contact evaluation by contact and index case characteristics. To investigate determinants of IPT initiation and completion, we used generalised linear mixed models. RESULTS: A total of 2323 contacts were reported by 662 index cases; the median number of contacts per case was four (IQR, 2-5). Evaluation at month 0 was completed by 99.2% (255/257) of contacts <5 and 98.1% (558/569) of contacts aged 5-19 years. Of 191 eligible contacts <5 years old, 70.2% (134) started IPT and 31.4% (42) completed it. Of 395 contacts 5-19 years old, 36.7% (145) started IPT and 32.4% (47) completed it. Factors associated to not starting IPT among contacts <5 years old were being a second-degree relative to the index case (OR 6.6 95CI% 2.6-16.5), not having received a tuberculin skin test (TST) (OR 3.9 95%CI 1.4-10.8), being contact of a smear-negative index case (OR 5.5 95%CI 2.0-15.1) and attending a low-caseload health facility (OR 2.8 95%CI 1.3-6.2). Factors associated to not starting IPT among 5-19 year-olds were age (OR 13.7 95%CI 5.9-32.0 for 16-19 vs. 5-7 years old), being a second-degree relative (OR 3.0 95%CI 1.6-5.6), not having received a TST (OR 5.4, 95%CI 2.5-11.8), being contact of a male index case (OR 2.1 95CI% 1.2-3.5), with smear-negative TB (OR 1.9 95%CI 1.0-3.6), and attending a high-caseload health facility (OR 2.1 95%CI 1.2-3.6). Factors associated to not completing IPT, among contacts who started, were not having received a TST (OR 3.4 95%CI 1.5-7.9 for <5 year-olds, and OR 4.3 95%CI 1.7-10.8 for those 5-19 years old), being contact of an index case with TB treatment outcome other than success (OR 9.3 95%CI 2.6-33.8 for <5 year-olds and OR 15.3 95%CI 1.9-125.8 for those 5-19 years old), and, only for those 5-19 years old, attending a health facility with high caseload (OR 3.2 95%CI 1.4-7.7) and a health facility with low proportion of TB cases with treatment success (OR 4.4 95%CI 1.9-10.2). CONCLUSIONS: We found partial compliance to TB contact investigation, and identified contact, index case and health facility-related factors associated to IPT start and completion that can guide the TB programme in increasing coverage and quality of this fundamental activity.

OBJECTIF: Les contacts des cas de tuberculose (TB) pulmonaire présentent un risque élevé d'infection à la TB et d'évolution vers la maladie. Les contacts étroits et familiaux et ceux de moins de 5 ans sont les plus à risque. Le traitement préventif à l'isoniazide (TPI) peut largement prévenir la maladie TB chez les personnes infectées. Nous avons mené une étude à Lima, au Pérou, pour déterminer le nombre de contacts proches et familiaux qui ont été évalués, qui ont commencé le TPI et qui l'ont achevé, ainsi que les facteurs associés au respect des directives nationales. MÉTHODES: Etude longitudinal rétrospective de tous les cas de TB diagnostiqués entre janvier 2015 et juillet 2016 dans 13 établissements de santé dans le sud de Lima. Les cartes de traitement, les registres de TB et les dossiers cliniques ont été examinés et des données sur les cas indice, l'investigation des contacts et les établissements de santé ont été extraites. Nous avons tabulé les fréquences d'évaluation des contacts par les caractéristiques des contacts et des cas indice. Pour étudier les déterminants de l'initiation et de l'achèvement du TPI, nous avons utilisé des modèles linéaires mixtes généralisés. RÉSULTATS: Au total, 2.323 contacts ont été rapportés par 662 cas indice; 70,2% des contacts âgés de moins de 5 ans ont commencé le TPI et 31,4% l'ont terminé, tandis que 36,7% des contacts âgés de 5 à 19 ans ont commencé le TPI et 32,4% l'ont terminé. Les facteurs associés au fait de ne pas commencer ou de terminer le TPI étaient: être un parent de second degré du cas indice, ne pas avoir reçu le test tuberculinique, être le contact d'un cas indice à frottis négatif et fréquenter un établissement de santé à faible charge de travail pour les moins de cinq ans contre fréquenter un établissement de santé à charge de travail élevée pour les contacts plus âgés. CONCLUSIONS: Nous avons constaté une compliance partielle à l'enquête sur les contacts de la TB, et avons identifié les facteurs liés aux contacts, aux cas indice et aux établissements de santé associés au début et à la fin du TPI qui peuvent guider le programme de TB dans l'augmentation de sa couverture et de sa qualité.

Impacto económico del dengue en pacientes y familiares / Economic impact of dengue on patients and families

Introducción: En Cuba no se han estudiado suficientemente los gastos de bolsillo y la pérdida de calidad de vida relacionada con la salud (de pacientes con dengue y sus familiares. Objetivo: Describir la afectación de la calidad de vida, los costos no médicos directos (gastos de bolsillo) e indirectos de pacientes hospitalizados con dengue y sus familiares. Método: Estudio de descripción de costos desde la perspectiva de pacientes y familiares, para los hospitalizados con dengue en el Clínico Quirúrgico Salvador Allende, en noviembre de 2013. En enero-febrero de 2014 se aplicó un cuestionario cerrado de 173 preguntas. Se calcularon la pérdida promedio de calidad de vida relacionada con la salud, los costos no médicos directos y los costos indirectos. Resultados: Durante el episodio de dengue el grupo de edad más afectado fue el de 30-44 años. Predominaron las mujeres (63,3 por ciento). La calidad de vida relacionada con la salud se afectó sensiblemente pasando como promedio de 86,9 el día antes de la enfermedad a 27,8 el día que las personas se sintieron más enfermas. En el momento de la entrevista, el 51 por ciento de los pacientes percibían que no se habían recuperado de la enfermedad. Los pacientes estuvieron hospitalizados como promedio 5 días. Los gastos de bolsillo de pacientes y familiares ascendieron a 61,24 CUC (IC95 por ciento 43,23-79,25 CUC), en que el 66,2 por ciento fue en alimentación y el 13,6 por ciento en transporte. Las pérdidas promedio de ingreso fueron de 25,30 CUC para los pacientes y 4,50 CUC para los familiares. Los costos totales promedio por paciente fueron de 89,25 CUC (IC95 por ciento 67,33-110,29 CUC). Conclusiones: Se evidenció la pérdida de calidad de vida como consecuencia del dengue. Los gastos de bolsillo fueron altos y representan tres veces el valor del salario medio de la Provincia La Habana(AU)

Introduction: Health-related loss of quality of life among dengue patients and their relatives, and unforeseen family expenses incurred for this reason, have not been sufficiently studied in Cuba. Objective: Describe the impact on quality of life, as well as the non-medical direct and indirect unforeseen expenses incurred by patients hospitalized with dengue and their relatives. Method: A cost analysis study was conducted based on data provided by patients hospitalized with dengue in Salvador Allende Clinical Surgical Hospital and their relatives in November 2013. A closed-ended questionnaire of 173 questions was applied in January-February 2014. Estimation was made of average health-related loss of quality of life, direct non-medical costs and indirect costs. Results: The 30-44 years age group was the most harshly affected during the episode. There was a predominance of the female sex (63.3 percent). Health-related quality of life decreased dramatically from an average 86.9 the day before the disease to 27.8 on the day when patients felt the worst. At the time of the interview, 51 percent of the patients perceived that they had not recovered from the disease. Mean hospital stay was 5 days. Unforeseen patient and family expenses rose to 61.24 CUC (CI 95 percent; 43.23-79.25 CUC), of which 66.2 percent was spent on food and 13.6 percent on transport. Average income loss was 25.30 CUC for patients and 4.50 CUC for relatives. Total average cost per patient was 89.25 CUC (CI 95 percent 67.33-110.29 CUC). Conclusions: Evidence was found of loss of quality of life as a result of dengue. Unforeseen expenses were high, representing three times the mean salary in the province of Havana(AU)

Opiniones de actores de salud sobre la estrategia de búsqueda activa de casos de tuberculosis / Opinions of health stakeholders on the active search strategy for tuberculosis cases

Introducción: La pesquisa activa de casos de tuberculosis en la Atención Primaria de Salud como parte del programa de control de la enfermedad en Cuba, tiene retos de implementación que requieren ser estudiados. Objetivo: Explorar las opiniones de los actores de salud involucrados en la implementación de la pesquisa activa de casos de tuberculosis en Las Tunas. Métodos: Se realizó un estudio cualitativo, en dos etapas, anidado en un estudio de intervención en Las Tunas. En la primera etapa (septiembre-diciembre, 2010) se entrevistaron médicos y enfermeras de la familia de los municipios Jobabo y Las Tunas; y en la segunda etapa (marzo, 2012), todos los jefes de programa (provincial y municipales) y un experto en tuberculosis. Se utilizaron categorías de análisis deductivas e inductivas. Resultados: La pesquisa activa de casos de tuberculosis se reconoció como un procedimiento novedoso asociado a la búsqueda de sintomáticos respiratorios en el hogar, la dispensarización y el trabajo con grupos vulnerables. Al inicio hubo barreras para la implementación del procedimiento, posteriormente fue aceptado. Las ventajas fueron: diagnóstico oportuno e incremento del número de casos pesquisados, entre otras. La falta de tiempo, el incremento en la carga de trabajo y la fluctuación del personal fueron las principales dificultades. Conclusiones: El estudio proporciona información valiosa para la implementación del procedimiento como parte del programa de control de la tuberculosis. Devela la brecha entre la percepción de los actores involucrados en la implementación de intervenciones en salud en estudios pilotos y la que tienen los implicados en su puesta en práctica(AU)

Introduction: The active case finding of tuberculosis in Primary Health Care as part of the disease control program in Cuba, has challenges at implementation that need to be studied. Objective: To explore the opinions of the health stakeholders involved in the implementation of active case finding of tuberculosis in Las Tunas. Methods: A qualitative study was carried out in two stages, nested in an intervention study in Las Tunas. In the first stage (September-December, 2010) family doctors and nurses in Jobabo and Las Tunas municipalities were interviewed; and in the second stage (March 2012), all program managers (provincial and municipal) and an expert on tuberculosis were interviewed. Deductive and inductive analysis categories were used. Results: The active case finding of tuberculosis was recognized as a novel procedure associated with the screening for respiratory symptoms among all family members during home visits, classification of the entire population into risk groups and working with vulnerable groups. At the beginning there were barriers to the implementation of this procedure, which was subsequently accepted. Timely diagnosis and increase in the number of cases investigated were the advantages, among others. The lack of time, the increase in workload and the staff turnover were the main difficulties. Conclusions: This study provides valuable information for implementing this procedure as part of tuberculosis control program. It reveals the gap between the perception of the stakeholders involved in the implementation of health interventions in pilot studies and from those engaged in their implementation(AU)

To the bone: Comment on "I wanted a skeleton they brought a prince": A qualitative investigation of factors mediating the implementation of a Performance Based Incentive program in Malawi.

Recently, McMahon and colleagues set out to build on a widely-used fidelity framework, assessing the role of moderating factors during the implementation of performance-based financing programs in Malawi. Their attempt draws again the attention to the importance of approaching real word implementation issues from a theoretical perspective. It also highlights the importance of fidelity assessment within process evaluation of health programs. In this comment we argue that theoretical developments in the field of implementation science in global health would benefit from an accurate understanding of existing conceptual frameworks as well as from taking into account all contemporary contributions.

Sostenibilidad de una estrategia cubana de empoderamiento comunitario para la prevención del dengue desde la perspectiva de sus actores claves / Sustainability of a Cuban community empowerment strategy for dengue fever prevention from the perspective of its key actors

Introducción: Las revisiones sistemáticas sobre intervenciones para la prevención del dengue señalan que existe poca evidencia sobre la sostenibilidad de estrategias participativas. Una estrategia cubana basada en el empoderamiento de la comunidad se implementó entre los años 2004-2007 y constó de cuatro componentes: organización, capacitación, trabajo comunitario, y la vigilancia de riesgos y comportamientos. Objetivo: Evaluar la percepción de sostenibilidad de la estrategia de empoderamiento comunitario para la prevención del dengue desde la perspectiva de los actores claves de su implementación. Métodos: Se realizó un estudio descriptivo de corte cualitativo anidado en el estudio experimental, de abril a septiembre de 2011. La sostenibilidad fue entendida como el uso continuado de los componentes de la estrategia y la ejecución de actividades a más de 3 años de concluida la etapa de implementación y evaluación, y el financiamiento externo de la investigación. Se realizaron entrevistas en profundidad a actores claves con un rol significativo durante las etapas de diseño e implementación. La información verbal se clasificó en categorías de análisis inductivas que emergieron de la lectura reiterada de los datos, y posteriormente se reclasificó y contrastó con indicadores operacionales de sostenibilidad de intervenciones de salud. Resultados: Los entrevistados identificaron transformaciones generadas por la estrategia (ejemplo: incremento de capacidades locales, crecimiento personal/profesional, nuevos estilos y organización del trabajo) a nivel de municipio, consejo popular y circunscripción. Desde la percepción la estrategia fue sostenible (91 referencias) y se aportaron nuevos elementos que enriquecen los indicadores operacionales de sostenibilidad utilizados, los cuales reconocen los beneficios de salud, y otros efectos directos a partir de la concepción de empoderamiento asumida por la propuesta. La construcción de capacidades fue valorada por los actores salud como el fortalecimiento de las competencias de los médicos y enfermeras de la familia, para guiar procesos participativos en las comunidades. Conclusiones: La perspectiva de los actores enriqueció el análisis de la sostenibilidad de la estrategia y reconoce la importancia del proceso de construcción de capacidades para empoderamiento desde la educación popular promovida durante la implementación para el mantenimiento de los resultados y su relación con los efectos informados por los actores(AU)

Introduction: Systematic reviews about dengue fever prevention interventions show that there is little evidence of the sustainability of participatory strategies. A Cuban community empowerment strategy was implemented between the years 2004 and 2007. It consisted of four components: organization, training, community work, and surveillance of risks and behavior. Objective: Evaluate the perception about sustainability of the community empowerment strategy for dengue fever prevention from the perspective of the key actors of its implementation. Methods: A nested descriptive qualitative experimental study was conducted from April to September 2011. Sustainability was understood as the continued use of the components of the strategy, the conduct of activities more than 3 years after completion of the implementation and evaluation stage, and external funding for the research. In-depth interviews were held with key actors playing a significant role during the stages of design and implementation. The information obtained was classified into inductive analysis categories emerging from the reiterated reading of the data, and was then reclassified and contrasted with operational sustainability indicators for health interventions. Results: Interviewees identified a number of changes brought about by the strategy, e.g. an increase in local capacities, personal / professional growth, new work styles and organization at the municipal, people's council and constituency levels. The strategy was perceived as sustainable (91 references), and new data were provided which enrich the operational sustainability indicators used and recognize the benefits to health care and other direct effects of the concept of empowerment underlying the proposal. The building of capacities was evaluated by health actors as the strengthening of family doctors' and nurses' competencies to lead participatory processes in the community. Conclusions: The views contributed by actors enriched the analysis about the sustainability of the strategy and recognized the importance of capacity building for empowerment based on community education, as fostered during the implementation stage, for the maintenance of results and their relationship to the effects reported by actors(AU)

Pérdida de calidad de vida y carga económica causada por dengue desde la perspectiva de pacientes y sus familiares / Loss of quality of life and economic burden caused by dengue fever from the perspective of patients and their families

Introducción: En Cuba hay pocos datos disponibles sobre la pérdida de calidad de vida relacionada con la salud y la carga económica para los pacientes de dengue y sus familiares. Objetivo: Describir la pérdida de calidad de vida relacionada con la salud y la carga económica del dengue para los pacientes y sus familiares. Métodos: Se aplicó un cuestionario a 92 pacientes adultos confirmados de dengue y hospitalizados en el Hospital Clínico Quirúrgico Docente Ambrosio Grillo de Santiago de Cuba, entre enero y octubre 2015; también se les aplicó a sus familias. Se calculó la pérdida promedio de calidad de vida a través de una escala analógica (0-100) y de los costos no médicos directos (gastos de bolsillo) e indirectos por paciente. Resultados: la pérdida global de calidad de vida fue de 67,9 por ciento en el peor momento de la enfermedad. El promedio de días autopercibidos hasta la recuperación fue 13,1. El promedio de visitas por paciente a los servicios ambulatorios antes de la hospitalización fue 1,3, y el policlínico resultó el servicio más utilizado. La estadía hospitalaria promedio fue 3,96 noches. Ningún enfermo presentó dengue grave. Los costos no médicos directos para los pacientes y sus familiares, fueron 7,95 USD (CUC). El 44,7 por ciento fue utilizado en transporte y 32,0 por ciento en alimentación, financiados principalmente con los ahorros personales y donaciones de familiares y amigos. Los costos indirectos promedio fueron 4,10 USD (CUC). Conclusión: Hubo una sustancial pérdida de calidad de vida durante la enfermedad. Los costos no médicos directos y los indirectos para los pacientes y familiares fueron bajos. La carga económica asumida por el gobierno es 12 veces mayor que estos(AU)

Introduction: Few data are available in Cuba about the loss of health-related quality of life and the economic burden caused by dengue fever to patients and their families. Objective: Describe the loss of health-related quality of life and the economic burden caused by dengue fever to patients and their families in Santiago de Cuba. Method: A questionnaire was applied to 92 adult patients with confirmed dengue fever admitted to Ambrosio Grillo Clinical Surgical University Hospital in Santiago de Cuba from January to October 2015. The questionnaire was also applied to their relatives. An analog scale (0-100) was used to estimate average loss of quality of life as well as indirect and direct non-medical costs expenses incurred by patients. Results: Global loss of quality of life was 67.9 percent at the worst stage of the condition. Average self-perceived days until recovery were 13.1. Average visits to outpatient services per patient before hospitalization were 1.3. The polyclinic was the most commonly used service. Average hospital stay was 3.96 nights. No patient had severe dengue fever. Direct non-medical expenses incurred by patients and their families were USD 7.95 (CUC), 44.7 percent of which were spent on transportation and 32.0 percent on food. These were mainly covered by personal savings and donations from relatives and friends. Average indirect expenses were USD 4.10 (CUC). Conclusion: There was considerable loss of quality of life during the disease. Patients and their families incurred low non-medical direct and indirect expenses. The economic burden undertaken by the government is 12 times as high(AU)

Assessment of hypertension management and control: a registry-based observational study in two municipalities in Cuba.

BACKGROUND: To determine the prevalence of hypertension treatment and control among hypertensive patients in the Cuban municipalities of Cardenas and Santiago and to explore the main associated predictors. METHODS: Cross-sectional study, with multistage cluster sampling, conducted between February 2012 and January 2013 in two Cuban municipalities. We interviewed and measured blood pressure in 1333 hypertensive patients aged 18 years or older. Hypertension control was defined as blood pressure lower than 140/90 mmHg. RESULTS: The mean age ± standard deviation (SD) of participants was 59.8 ± 14 years, the mean systolic and diastolic blood pressure ± SD was 130.0 ± 14.4 and 83.1 ± 9.0 mmHg respectively. The majority of patients (91, 95%CI 90-93) were on pharmacological treatment, 49% with a combination of 2 or more classes of drugs. Among diagnosed hypertensive patients 58% (95%CI 55-61) had controlled hypertension. There was no association between hypertension control and gender, age and socio-economic condition. Levels of hypertension control depended on health area and control furthermore was positively associated with post-primary education, not being obese and white ethnicity: adjusted Odds Ratio (95% CI) 1.71 (1.26-2.34), 1.43 (1.09-1.88) and 1.41 (1.09-1.81) respectively. CONCLUSIONS: The observed figures are outstanding at the international level and illustrate that hypertension treatment and control are achievable in a resource-constrained setting such as Cuba. The country's primary health care approach and social equity in access to health care can be seen as key determinants of this success. Nevertheless, there is still room for improvement, as over a third of patients did not have controlled hypertension.